Despite decades of basic and clinical research, colorectal cancer remains one of mankind's most deadly non-communicable diseases. According to the GLOBOCAN Project of the World Health Organization's International Agency for Research on Cancer, it was estimated that in 2008 the incidence of colorectal cancer was over 1.2 million and that in the same year more than 600 thousand people were killed by the disease. While much has been learned recently regarding how colorectal cancer works at the molecular level, clinicians still rely on therapeutic modalities such as surgery, radiation and chemotherapy that would have been familiar to oncologists of a generation ago. Early diagnosis, made possible by advances in imaging technology and molecular diagnostics, factors greatly in the success of any treatment. Although the efficacy of all these treatments has improved over the years, the improvement in cure rates and the increase in longevity have been incremental. Even the new targeted therapies resulting from the revolution in molecular oncology have, for the most part, improved outcomes only modestly.
Two of the most challenging aspects of managing colorectal cancer patients are metastasis and recurrence.
Metastasis occurs when the colorectal cancer spreads to distant organs from the primary tumor. While it is often possible to resect the primary tumor, it is the metastases that frequently end up killing the patient because they become too numerous or entwined with healthy host tissue to treat surgically. According to the American Cancer Society, the five year survival rate in the United States for patients diagnosed with Stage IIIC colon cancer between 1998 and 2000 was 28%, which dropped to only 6% at Stage IV (i.e., metastatic colorectal cancer).
Recurrence is the phenomenon by which colorectal cancer returns after initially responding to treatment and apparently disappearing. Apart from the emotional toll inflicted on patients and their families, recurrence is problematic because the returning cancer may be less responsive to the therapy or therapies that were effective to fight the first cancer. For other patients, prior treatments for the first cancer may have caused irreversible side effects, such as cardiac or neurological damage. In such patients, the risks of using the same therapy to fight the recurrent cancer may be too great. Under these circumstances, a patient may have fewer treatment options with a concomitantly greater risk of mortality.
While improvements in radiation treatment, chemotherapy and the advent of targeted therapies have increased the longevity of patients stricken by colorectal cancer, many such patients continue to die within months to a few years after their diagnosis. An urgent need therefore exists for new treatments effective against metastatic colorectal cancer and recurrence of colorectal cancer.